Literature DB >> 19239365

Predicting the response to combination antiretroviral therapy: retrospective validation of geno2pheno-THEO on a large clinical database.

André Altmann1, Martin Däumer, Niko Beerenwinkel, Yardena Peres, Eugen Schülter, Joachim Büch, Soo-Yon Rhee, Anders Sönnerborg, W Jeffrey Fessel, Robert W Shafer, Maurizio Zazzi, Rolf Kaiser, Thomas Lengauer.   

Abstract

BACKGROUND: Expert-based genotypic interpretation systems are standard methods for guiding treatment selection for patients infected with human immunodeficiency virus type 1. We previously introduced the software pipeline geno2pheno-THEO (g2p-THEO), which on the basis of viral sequence predicts the response to treatment with a combination of antiretroviral compounds by applying methods from statistical learning and the estimated potential of the virus to escape from drug pressure.
METHODS: We retrospectively validated the statistical model used by g2p-THEO in approximately 7600 independent treatment-sequence pairs extracted from the EuResist integrated database, ranging from 1990 to 2007. Results were compared with the 3 most widely used expert-based interpretation systems: Stanford HIVdb, ANRS, and Rega.
RESULTS: The difference in receiver operating characteristic curves between g2p-THEO and expert-based approaches was significant (P < .001; paired Wilcoxon test). Indeed, at 80% specificity, g2p-THEO found 16.2%-19.8% more successful regimens than did the expert-based approaches. The increased performance of g2p-THEO was confirmed in a 2001-2007 data set from which most obsolete therapies had been removed.
CONCLUSION: Finding drug combinations that increase the chances of therapeutic success is the main reason for using decision support systems. The present analysis of a large data set derived from clinical practice demonstrates that g2p-THEO solves this task significantly better than state-of-the-art expert-based systems. The tool is available at http://www.geno2pheno.org.

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Year:  2009        PMID: 19239365     DOI: 10.1086/597305

Source DB:  PubMed          Journal:  J Infect Dis        ISSN: 0022-1899            Impact factor:   5.226


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